Most anti-HIV regimens include a non-nucleoside reverse transcriptase inhibitor (NNRTI); however, some individuals fail on these regimens. The purpose of this study is to evaluate the safety and effectiveness of the protease inhibitor (PI) lopinavir/ritonavir (LPV/r) in HIV infected individuals who are failing an anti-HIV regimen that includes an NNRTI.

Probability of Grade 3 or 4 sign or symptom, or laboratory toxicity over 24 weeks on study using Kaplan-Meier estimates of the cumulative probability of Grade 3 or 4 sign or symptom, or laboratory toxicity at week 24. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

Secondary Outcome Measures:

Number of Screened Subjects With at Least One NNRTI, or NRTI-associated Resistance Mutation at A5230 Screening. [ Time Frame: Screening ] [ Designated as safety issue: No ]

Number of screened subjects with at least one NNRTI, or NRTI-associated resistance mutation. Resistance interpretations used the November 30, 2011 Stanford algorithm.

Time to Treatment Failure, Defined as the First Occurrence of Death, Disease Progression, or Virologic Failure. [ Time Frame: Study entry to Week 104 ] [ Designated as safety issue: Yes ]

25th percentile in weeks from study entry to treatment failure, defined as the first occurrence of death, disease progression, or virologic failure. Virologic failure was defined as HIV-1 >= 400 copies/mL after week 24 or 2 consecutive HIV-1 RNA >= 400 copies/mL after week 16 following suppression on LPV/r monotherapy.

Number of Participants With Study-targeted Diagnoses and Clinical Events [ Time Frame: Study entry to week 104 ] [ Designated as safety issue: No ]

The percentage of subjects reporting never missing medications in the last month.

Time to First New Grade 3 or 4 Sign or Symptom or Laboratory Toxicity Following LPV/r Intensification [ Time Frame: From LPV/r intensification to week 104 ] [ Designated as safety issue: Yes ]

25th percentile in weeks from study entry to first new grade 3 or 4 sign or symptom or laboratory toxicity following LPV/r intensification. Grading of adverse events (signs and symptoms and laboratory toxicities) was according to Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, December 2004.

Level of HIV-1 RNA as Ascertained From Paired DBS and Plasma [ Time Frame: At study entry and weeks 24 and 48 ] [ Designated as safety issue: No ]

Participants will receive lopinavir/ritonavir twice daily for up to 104 weeks. Upon confirmation of virologic failure, emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) once a day will be added to their regimen.

Drug: Emtricitabine/Tenofovir disoproxil fumarate

Once daily

Other Name: Truvada

Drug: Lopinavir/Ritonavir

Twice daily

Other Name: Kaletra, Aluvia

Detailed Description:

Standard effective antiretroviral therapy for HIV infected individuals includes three-drug combinations of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a PI or an NNRTI. However, three-drug regimens may not be ideal in resource-limited settings, where viral load and resistance testing may not be readily available. The purpose of this study is to evaluate the safety and efficacy of the PI LPV/r alone in treatment-experienced, PI-naive HIV infected individuals who are experiencing virologic failure on three-drug regimens.

This study will last 104 weeks. All participants will receive LPV/r twice daily for up to 104 weeks. Participants who experience virologic failure will receive emtricitabine/tenofovir disoproxil fumarate once daily in addition to LPV/r twice daily for the remainder of the study.

There will be 16 study visits for participants on LPV/r monotherapy and 12 study visits for participants who have intensified LPV/r with emtricitabine/tenofovir disoproxil fumarate. Blood collection and clinical assessment will occur at all visits; urine collection and resistance testing will occur at selected visits.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for Step 1 Participants:

HIV infected

Continuous treatment with a three-drug, NNRTI-containing regimen for at least 6 months prior to study entry

Viral load of 1,000 copies/ml or greater and less or equal to 200,000 copies/ml obtained within 30 days of study entry

Negative pregnancy test within 48 hours of study entry

Willing to use acceptable forms of contraception for the duration of the study

Laboratory values obtained within 30 days of study entry:

Hemoglobin greater or equal to 8.0 g/dL

Platelet count greater or equal to 50,000/mm3

Estimated Creatinine Clearance greater or equal to 60 mL/min x ULN

AST (SGOT), ALT (SGPT) and alkaline phosphatase < 3 x ULN

Total bilirubin less or equal to 2.5 x ULN

Ability and willingness of participant or legal guardian/representative to give informed consent

Willing to use acceptable forms of contraception for the duration of the study

Exclusion Criteria for All Participants:

Breastfeeding

Known allergy or sensitivity to study drugs

Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with study adherence to study requirements

History of chronic hepatitis B infection

Exclusion Criteria for Step I Participants:

Prior use of any protease inhibitor treatment

Acute therapy for any serious medical condition within 14 days of study entry. For ongoing or chronic therapy, the participant must be on the treatment regimen for at least 14 days, and clinically stable prior to entry. If a potential participant has TB and has received treatment for more than 2 weeks, the TB treatment would have to be modified to include a rifabutin-containing regimen. TB compatible syndromes will also be carefully evaluated prior to entry.

Exclusion Criteria for Step 2 Participants:

- Active opportunistic infection, including tuberculosis (TB)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357552